Psilocybin for anorexia nervosa: efficacy, safety, and durability of clinical effects: a systematic review of clinical trials

Introduction: Anorexia nervosa is a severe psychiatric disorder with substantial morbidity and limited pharmacological treatment options. Psilocybin-assisted interventions have emerged as a potential novel approach, but evidence specific to anorexia nervosa remains limited. Objective: To evaluate the efficacy, safety, tolerability, and durability of psilocybin-based interventions in adults with anorexia nervosa. Methods: Registered in the International Prospective Register of Systematic Reviews (PROSPERO number CRD420261479321). The review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. PubMed, Scopus, Web of Science, and the Cochrane Library were systematically searched. Prospective clinical trials evaluating psilocybin in adults with anorexia nervosa were eligible. Outcomes included eating-disorder psychopathology, associated psychiatric symptoms, weight-related outcomes, safety, acceptability, and durability. Findings were synthesized narratively according to study design and outcome domain. Results: Two independent uncontrolled prospective trials involving 31 participants met the inclusion criteria. Psilocybin administration was associated with improvements in global and domain-specific eating-disorder psychopathology, motivation for recovery, body-image anxiety, anxiety symptoms, eating-related preoccupations, and functional impairment, although findings were heterogeneous across outcomes. Some improvements persisted beyond the immediate treatment period, with follow-up extending to 12 months in one study. Acute tolerability was generally acceptable, although serious psychiatric events and hypoglycemia were reported. The absence of randomized comparators and the small, highly selected samples precluded causal inference and quantitative meta-analysis. Conclusion: Psilocybin-assisted interventions show promising preliminary clinical signals in anorexia nervosa, including improvements in eating-disorder psychopathology and selected associated outcomes. However, current evidence remains insufficient to establish efficacy or generalizable safety. Well-powered randomized controlled trials with rigorous medical monitoring and longer follow-up are warranted.